Introduction: Numerous population studies have linked elevated concentration of total cholesterol or LDL–cholesterol in plasma with increased incidence of atherosclerotic events. It has further been shown that the clinical complications of atherosclerosis could be diminished and life prolonged when plasma lipids are lowered by hypocholesterolemic agents. The leaves of Moringa oleifera Lam (Moringaceae) are used in many cultures as a hypocholesterolemic agent in obese patients. Taking into consideration that B6.129P2-Apoetm1Unc/J mice exhibit a marked increase in plasma cholesterol level and develop atherosclerotic lesions resembling those seen in humans; the main objective of our study was to evaluate the hypocholesterolemic and anti-atherosclerotic effects of Moringa oleifera leaf decoction in ApoE KO mice. Material and Methods: Males and females B6.129P2-Apoetm1Unc/J KO with 4 – 8 weeks of age were fed ad libitum with normal diet. The half of the animals was fed with leaf decoction of Moringa oleifera during 90 days and the other served as control. C57Bl/6 mice were used as control. Body weight, food consumption, haematological and biochemical parameters, relative weight of the organs and aortic atherosclerotic lesions were measured. Results: It was found that administration of Moringa oleifera leaf decoction decreased the cholesterol increases in ApoE KO mice serum in comparison with control group, while no changes were found in wild type mice (C57Bl/6). Atherosclerotic plaque formation in aorta was also reduced approximately 35 % in treated ApoE KO mice. The behavior of the body weights showed gain of weight in all animals from the beginning until the end of the study without any obvious signs of toxicity.Conclusions: It was concluded that the leaves of Moringa oleifera have hypocholesterolemic and anti-atherosclerotic activity in B6.129P2-Apoetm1Unc/J mice and that there is valid pharmacological basis for employing them for this purpose in humans.